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1、JOURNALOFVIROLOGY,Aug.2006,p.78947901Vol.80,No.160022-538X/06/$08.000doi:10.1128/JVI.00467-06Copyright?2006,AmericanSocietyforMicrobiology.AllRightsReserved.CrystalStructureofNonstructuralProtein10fromtheSevereAcuteRespiratorySyndromeCoronavirusRevealsaNovelFoldwithTwoZinc-BindingMotifs1,21,
2、21,23JeremiahS.Joseph,KumarSinghSaikatendu,VanithaSubramanian,BenjaminW.Neuman,12212AlexeiBrooun,MarkGrif?th,KinMoy,ManeeshK.Yadav,JeffreyVelasquez,321MichaelJ.Buchmeier,RaymondC.Stevens,andPeterKuhn*123DepartmentofCellBiology,DepartmentofMolecularBiology,andDepartmentofNeuropharmacology,TheS
3、crippsResearchInstitute,10550N.TorreyPinesRoad,LaJolla,California92037Received6March2006/Accepted23May2006Thesevereacuterespiratorysyndromecoronavirus(SARS-CoV)possessesalarge29.7-kbpositive-strandedRNAgenome.The?rstopenreadingframeencodesreplicasepolyproteins1aand1ab,whicharecleavedtogenerat
4、e16“nonstructural”proteins,nsp1tonsp16,involvedinviralreplicationand/orRNAprocessing.Amongthese,nsp10playsacriticalroleinminus-strandRNAsynthesisinarelatedcoronavirus,murinehepatitisvirus.Here,wereportthecrystalstructureofSARS-CoVnsp10ataresolutionof1.8?asdeterminedbysingle-wavelengthanomalou
5、sdispersionusingphasesderivedfromhexatantalumdodecabromide.nsp10isasingledomainproteinconsistingofapairofantiparallelN-terminalhelicesstackedagainstanirregular-sheet,acoil-richCterminus,andtwoZn?ngers.nsp10representsanovelfoldandisthe?rststructuralrepresentativeofthisfamilyofZn?ngerproteinsf
6、oundsofarexclusivelyincoronaviruses.The?rstZn?nger2coordinatesaZnioninauniqueconformation.ThesecondZn?nger,withfourcysteines,isadistant2memberofthe“gag-knucklefoldgroup”ofZn-bindingdomainsandappearstomaintainthestructuralintegrityoftheC-terminaltail.Adistinctclusteringofbasicresiduesonthepr
7、oteinsurfacesuggestsanucleicacid-bindingfunction.Gelshiftassaysindicatethatinisolation,nsp10bindssingle-anddouble-strandedRNAandDNAwithhigh-micromolaraf?nityandwithoutobvioussequencespeci?city.Itispossiblethatnsp10functionswithinalargerRNA-bi